TCF-II, tumor cytotoxic factor derived from human fibroblast, is a novel anti-tumor protein which is different from any other proteins so far reported. The inventors succeeded in cDNA cloning of this protein, deduced its entire amino-acid sequence and confirmed the usefulness. This novel anti-tumor protein and its cDNA were disclosed in W090/10651. They were designated as TCF-II. In this invention, the glycoprotein which has the amino-acid sequence disclosed in W090/10651 is called TCF. TCF is a substance which has been called TCF-II.
TCF has both strong cytotoxic activity against tumor cells and growth stimulating activity for normal cells. And it has been confirmed that TCF is member of a family including HGF, a growth factor for hepatocytes. The. molecular weight of TCF is 78000.+-.2000 daltons and/or 74000.+-.2000 daltons on SDS polyacrylamide gel electrophoresis. Under reducing conditions, it showed a polypeptide band called A chain with a molecular mass of 52000.+-.2000 daltons and two polypeptide bands called B chain and/or C chain with molecular masses of 30000.+-.2000 daltons and/or 26000.+-.2000 daltons, respectively.
Because TCF is a growth factor for hepatocytes, application to liver regeneration after hepatectomy has been examined. Since biological half-life of TCF is very short, attempts have been made to obtain more effective modified TCFs with prolonged biological half-lives.
Relationship between oligosaccharide chains and serum half-lives has been investigated in some glycoproteins including erythropoietin. The investigations have demonstrated that glycoproteins with slightly different structure in oligosaccharide chains and with different biological activities can be synthesized from the same gene. It was known that glycosylated erythropoietin is different in the biological activities from non-glycosylated one. However, about the relationship between oligosaccharide chains and biological activities of TCF little was known.